大黄素联用吉西他滨对胰腺癌细胞 Bxpc －3裸鼠移植瘤的抑制作用

摘要

Objective To investigate the enhanced gemcitabine-induced apoptosis by emodin and the possi-ble therapeutic mechanism.Methods Human pancreatic carcinoma Bxpc-3 cells were cultured and the murine xeno-graft model bearing human pancreatic carcinoma was established.Then the mice were randomly divided into control group,emodin group,gemcitabine group and emodin combined with gemcitabine group.Body weight of mice、the tumor volume and tumor weight were measured during the study.And Immunohistochemistry(IHC)was used to detect the variance of the apoptotsis relative protein expression such as NF-κB、Bcl-2 and Active caspase 3.Results After the last administrations,the average weight of nude mice in gemcitabine group decreased significantly compared with the control group,and the nude mice weight in the combined therapy group had no significant decrease compared with the control group.And the mean tumor volume and tumor weight in combined administration group was significantly de-creased compared to the other groups.Immunohistochemistry(IHC)analysis showed the expression of NF-κB、bcl-2 proteins was significantly decreased in the combined administration group compared to the other gourps.Active caspase 3 was significantly increased compared to the other gourps.Conclusion Emodin can enhance the antitumor effect of gemcitabine in the growth of the xenografts of human pancreatic cancer Bxpc-3 cells in nude mice,whose mechanisms may be related to the downregulation of NF-κB and Bcl-2.%目的：探讨大黄素增强吉西他滨对胰腺癌细胞 Bxpc-3裸鼠移植瘤的促凋亡作用及其可能的作用机制。方法在培养人胰腺癌 Bxpc-3细胞的基础上建立荷瘤模型，荷瘤裸鼠用随机区组设计分配方法分为四组：0．9％氯化钠注射溶液组（N 组）：腹腔注射0．9％氯化钠注射溶液0．2 mL，大 黄 素 组（E 组，40 mg／kg），吉西他滨组（G 组，125 mg／kg），联合组（E ＋G 组，大黄素40 mg／kg 和吉西他滨80 mg／kg）。用药均采用腹腔注射。用药过程观测裸鼠体质量、肿瘤体积和瘤重的变化。用免疫组织化学染色法来检测移植瘤组织中凋亡相关蛋白 NF-κB、Bcl-2和 Active caspase 3表达的变化。结果给药结束后，吉西他滨组的裸鼠平均体质量和对照组相比显著减小，而联合组中裸鼠平均体质量和对照组相比差异无统计学意义；联合组移植瘤平均体积和瘤重均明显比其他组小；E ＋G 组的 NF-κB、Bcl-2的表达与其余各组比较均明显降低，联合组中的 Active caspase 3的表达和其余各组相比明显增多。结论大黄素可显著提高吉西他滨对 Bxpc-3胰腺癌细胞裸鼠移植瘤的抑瘤作用，其作用机制可能为大黄素抑制凋亡抑制基因 NF-κB、Bcl-2的表达从而促进胰腺癌细胞的凋亡。